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Radioimmunoconjugates for targeted alpha therapy

Active Publication Date: 2007-07-12
EURO COMMUNITY AS PRESENTED BY THE EURO COMMISSION THE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0020] It is to be further noted that the present radioimmunoconjugate is of particular applicability for adjunctive therapy for early metastatic cancer, or cancer at the minimum residual stage. For example, high risk cancer patients shall be treated with the radioimmunoconjugates immediately after removal of the primary tumour to selectively kill isolated cancer cells or small nests of such cells at the preangioge

Problems solved by technology

During radioactive decay, photons, electrons or even heavier particles are emitted and damage or kill cells along their trajectory.
These have a relative low linear energy transfer (LET) and a long range in tissues, so their decay energy is only partially absorbed by the cancerous cells; the remainder attacks healthy cells in an undesirable manner.
The design of radioimmunoconjugates is thus a complex matter and the actual efficiency of a radioimmunoconjugate can in fact only be validated by testing in pre-clinical and clinical trials.

Method used

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Examples

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examples

[0037] a) Production of the Radionuclides

[0038] The rare earth nuclide Tb-149 can be produced on a tandem, cyclotron or linear accelerator using high energy heavy ions such as boron or carbon or nitrogen ions to bombard targets of Praseodymium, e.g. Pr(12C,4n) or Neodymium Nd(12C,5n) or at GeV energies using proton induced spallation.

[0039] At-211 can be produced with 26 MeV alphas bombarding a Bi target.

[0040] Bi-213 is available from the decay of the mother radioisotope Ac-225. This is typically done by loading the mother radionuclide Ac-225 on a separation column (employing ion exchange resin or extraction chromatographic material) of a so-called radionuclide generator.

[0041] Bi-212 is available from the decay of the parent radioisotope Th-228.

[0042] Ac-225 can be obtained by neutron or proton bombardment of Ra-226 targets (see e.g. EP 0 752 710-B1 and EP 0 962 942-B1). Alternately, Ac-225 can be obtained by radioactive decay of Th-229, which itself can be produced by irradi...

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Abstract

A radioimmunoconjugate for targeted alpha therapy comprises an alpha-emitter (e.g. Bi-213) linked to the monoclonal antibody C595. This radioimmunoconjugate is widely applicable in cancer therapy and is particularly efficient for treatment of pancreatic and prostate cancer, as well as for breast and ovarian cancer.

Description

TECHNICAL FIELD [0001] The present invention generally relates to radioimmunoconjugates for targeted alpha-immunotherapy. BACKGROUND ART [0002] The treatment of cancer by radio-immunotherapy involves injecting the patient with a radioactive isotope ‘bullet’ connected to a specific cancer cell vector such as a monoclonal antibody, with the aim of selectively destroying targeted tumour cells. During radioactive decay, photons, electrons or even heavier particles are emitted and damage or kill cells along their trajectory. [0003] Radio-immunotherapy (RIT) is still a relatively new modality for cancer therapy, which started using beta-emitting radionuclides. These have a relative low linear energy transfer (LET) and a long range in tissues, so their decay energy is only partially absorbed by the cancerous cells; the remainder attacks healthy cells in an undesirable manner. [0004] As a result, the focus of research shifted to radionuclides emitting alpha particles, which have high linear...

Claims

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Application Information

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IPC IPC(8): A61K51/00C07K16/46A61K51/10A61P35/00
CPCA61K51/1093A61P35/00
Inventor ALLEN, BARRYRIZVI, SYEDLI, YONGQU, CHANG FA
Owner EURO COMMUNITY AS PRESENTED BY THE EURO COMMISSION THE